Nucleophilic Addition to the Carbonyl Group: Factors Affecting Reactivity

The ability of carbonyl compounds such as aldehydes and ketones to undergo nucleophilic addition reactions depends upon two important parameters, namely steric and electronic factors.

The steric factor affects the transition state of the nucleophilic addition reaction. Since a ketone has two alkyl groups around the carbonyl group (Figure 1b), its tetrahedral transition state is more crowded than the transition state of an aldehyde. The steric crowding increases the repulsion between the nucleophile and the alkyl groups in a ketone, leading to a raised energy of the ketone’s transition state. Therefore ketones are less reactive towards a nucleophilic attack in comparison to aldehydes. Additionally, as the size of the alkyl group increases, the reactivity of the molecule decreases because of the stronger steric repulsion in the transition state.

Apart from the steric factors, the reactivity is also influenced by the electron-donating effects of the alkyl groups. Ketones, having two electron-donating alkyl groups, experience a slightly reduced electrophilicity of the carbonyl carbon and thereby a lower reactivity towards a nucleophilic attack. In comparsion, the carbonyl carbon of the aldehyde is more prone to a nucleophilic attack, due to the presence of only one alkyl group. Interestingly, if an electron-withdrawing group is attached to the carbonyl carbon of either aldehyde or ketone, the carbonyl carbon’s electrophilicity is enhanced, increasing the reactivity towards a nucleophilic addition.

These reactivity differences can be experimentally determined using the formation enthalpy values. The higher the formation enthalpy values, the greater the stability of the compound and the lower its reactivity. For instance, between propanal and acetone, acetone has a higher formation enthalpy value and is less reactive as predicted by the electronic and steric factors.